One of the key challenges in orthodontics is the long treatment time necessary to achieve adequate results. Developing solutions to this challenge would have a positive impact on the quality of orthodontic care. In an attempt to move teeth faster, two strategies had been explored, namely local injections of biomolecules such as PGE2 and RANKL, and surgical severance (decortication) of the alveolar bone. However, both methods have failed to be translated to clinical application because of their invasiveness. The long-term goal of this project is to apply mechanical vibration (MV) to enhance tooth movement in orthodontic patients to shorten overall treatment time. The overall objective of this project is to use a mouse model to better understand the effect of MV on orthodontic tooth movement (OTM) and to determine its effect on alveolar bone modeling as the underlying mechanism of this effect. OTM is a process of mechanically-induced modeling of periodontium wherein bone is resorbed on the compression side and formed on the tension side of the periodontal ligament (PDL). No matter how light a force is, due to the irregular surfaces of the dental root and alveolar socket wall, the blood vessels in the PDL are occluded to some extent, inducing a tissue damage called hyalinization and leading to a lag phase of OTM. Thus, increasing tooth motion without blood vessel blockage is the key to move teeth faster. One of the possible means of achieving this is to use MV to modify static orthodontic forces. Recently, resonance vibration has been shown to be able to increase OTM rate in rats (Nishimura, 2008). The mechanism leading to the effect, however, is not known. Our preliminary data in mice suggest increased OTM with MV. Based on these findings, we hypothesize that MV may be a powerful and non-invasive tool to enhance OTM and that the mechanism of this effect may be through the modulation of the OPG/RANKL and SOST signaling pathways. To test our hypotheses, we plan to complete the following specific aims (SA). SA1: To determine the effects of MV at physiological frequency on OTM rates. To target this specific aim, we will apply MV to the orthodontically moved maxillary 1st molars in mice every 3 days for 28 consecutive days. To quantify the rate of OTM, weekly radiographs and a microCT scan on the 28th day will be taken. Our working hypothesis is that MV enhances OTM rates. SA2: To prove that MV affects OTM by altering the modeling rates of the alveolar bone. To target this specific aim, undecalcified tissues will be sectioned to evaluate the histomorphometric parameters as well as histological staining. To gain insights into the mechanism, the production profile of three key bone metabolic regulatory molecules - OPG, RANKL and SOST proteins will be examined Immunohistochemically. Our working hypothesis is that MV increases bone resorption at the compression side of PDL by increasing the ratio of RANKL/OPG and the production of SOST protein. If our hypotheses prove to be correct, the logical next step will be to further investigate the mechanism of this phenomenon as well as to translate the current findings from animals to human clinical studies.